NCT04149275
Withdrawn
Phase 2
A Phase II Single Arm Study of Cabozantinib Plus Nivolumab and Ipilimumab in Women With Recurrent Gynecologic Carcinosarcoma
Overview
- Phase
- Phase 2
- Intervention
- Cabozantinib
- Conditions
- Carcinosarcoma of Ovary
- Sponsor
- University of Alabama at Birmingham
- Locations
- 1
- Primary Endpoint
- Percent progression free survival according to RECIST v1.1
- Status
- Withdrawn
- Last Updated
- 5 years ago
Overview
Brief Summary
The purpose of this study is to test the safety of Cabozantinib in combination with Nivolumab and Ipilimumab and see what affects that this combination treatment has on those with recurrent carcinosarcomas.
Detailed Description
Primary Objectives: • To estimate the proportion of patients with recurrent carcinosarcoma, who survive progression-free for at least 6 months, treated with cabozantinib + nivolumab + ipilimumab in the second-line and beyond setting (per iRECIST). Secondary Objectives: * To evaluate time to progression (Time Frame: From the date the patient received the first study treatment dose until the date of first documented progression, assessed up to 2 years). Progression Free Survival (PFS) according to iRECIST. * To determine the nature and degree of toxicity of cabozantinib + nivolumab + ipilimumab in this cohort of patients. Toxicity according to CTCAE v4.03 * To estimate the overall survival (OS) of patients with carcinosarcoma treated with cabozantinib + nivolumab + ipilimumab Exploratory Objectives: * To determine expression of biomarkers, which will include PD-L1 and MET expression by IHC, MSI status by NGS, and other relevant potential biomarkers. * To determine whether these marker expression levels alone or in combination are associated with response, PFS, and/or overall survival.
Investigators
Rebecca Arend
Principal Investigator
University of Alabama at Birmingham
Eligibility Criteria
Inclusion Criteria
- •Histologically confirmed diagnosis of carcinosarcoma (independent of organ of origin).
- •Received at least one prior chemotherapy regimen for their cancer.
- •Must have measurable or evaluable lesion defined by iRECIST.
- •Recovery to baseline or ≤ Grade 1 CTCAE v4 from toxicities related to any prior treatments, unless AE(s) are clinically non-significant and/or stable on supportive therapy.
- •Karnofsky performance status greater than or equal to 70% or ECOG PS = 0\~2
- •Age ≥ 18 years.
- •Adequate organ and marrow function, based upon meeting all of the following laboratory criteria within 14 days before first dose of study treatment:
- •Absolute neutrophil count (ANC) ≥ 1500/mm3 (≥ 1.5 GI/L) without granulocyte colony-stimulating factor support.
- •White blood cell count ≥ 2500/mm3 (≥ 2.5 GI/L).
- •Platelets ≥ 100,000/mm3 (≥ 100 GI/L) without transfusion.
Exclusion Criteria
- •Prior treatment with cabozantinib.
- •Receipt of any type of small molecule kinase inhibitor (including investigational kinase inhibitor) within 2 weeks before first dose of study treatment.
- •Receipt of any type of cytotoxic, biologic or other systemic anticancer therapy (including investigational) within 4 weeks before first dose of study treatment.
- •Radiation therapy for bone metastasis within 2 weeks, any other radiation therapy within 4 weeks before first dose of study treatment. Systemic treatment with radionuclides within 6 weeks before the first dose of study treatment. Subjects with clinically relevant ongoing complications from prior radiation therapy are not eligible.
- •Known brain metastases or cranial epidural disease unless adequately treated with radiotherapy and/or surgery (including radiosurgery) and stable for at least 4 weeks before first dose of study treatment. Eligible subjects must be neurologically asymptomatic and without corticosteroid treatment at the time of first dose of study treatment.
- •Concomitant anticoagulation with oral anticoagulants (eg, warfarin, direct thrombin and Factor Xa inhibitors) or platelet inhibitors (eg, clopidogrel). Allowed anticoagulants are the following:
- •Low-dose aspirin for cardioprotection (per local applicable guidelines) is permitted.
- •Low-dose low molecular weight heparins (LMWH) are permitted.
- •Anticoagulation with therapeutic doses of LMWH is allowed in subjects without known brain metastases who are on a stable dose of LMWH for at least 6 weeks before first dose of study treatment, and who have had no clinically significant hemorrhagic complications from the anticoagulation regimen or the tumor.
- •The subject has prothrombin time (PT)/INR or partial thromboplastin time (PTT) test ≥ 1.3 x the laboratory ULN within 7 days before the first dose of study treatment.
Arms & Interventions
Cabozantinib + Nivolumab + Ipilimumab
All recurrent carcinosarcomas
Intervention: Cabozantinib
Cabozantinib + Nivolumab + Ipilimumab
All recurrent carcinosarcomas
Intervention: Ipilimumab
Cabozantinib + Nivolumab + Ipilimumab
All recurrent carcinosarcomas
Intervention: Nivolumab
Outcomes
Primary Outcomes
Percent progression free survival according to RECIST v1.1
Time Frame: Baseline through 6 months
To estimate the proportion of patients with recurrent carcinosarcoma, who survive progression-free for at least 6 months, treated with cabozantinib + nivolumab + ipilimumab in the second-line and beyond setting (per iRECIST).
Secondary Outcomes
- Percent time to progression according to RECIST v1.1(Baseline through 2 years)
- Percent overall survival according to RECIST v1.1(Baseline through 2 years)
- Percent of patients with toxicity according to CTCAE v4.03(Baseline through 2 years)
Study Sites (1)
Loading locations...
Similar Trials
Recruiting
Phase 2
Study of Cabozantinib and Nivolumab in Metastatic Castration Resistant Prostate CancerCastration-resistant Prostate CancerMetastatic CancerNCT05502315Rana McKay, MD47
Active, not recruiting
Phase 1
Cabozantinib S-malate and Nivolumab With or Without Ipilimumab in Treating Patients With Metastatic Genitourinary TumorsBladder Small Cell Neuroendocrine CarcinomaBladder Squamous Cell CarcinomaBladder Urothelial CarcinomaClear Cell Renal Cell CarcinomaInvasive Bladder Plasmacytoid Urothelial CarcinomaInvasive Bladder Sarcomatoid Urothelial CarcinomaInvasive Sarcomatoid Urothelial CarcinomaKidney Medullary CarcinomaMalignant Genitourinary System NeoplasmMalignant Solid NeoplasmPenile CarcinomaPenile Squamous Cell CarcinomaRenal Cell CarcinomaRenal Pelvis Urothelial CarcinomaSarcomatoid Renal Cell CarcinomaStage III Bladder Cancer AJCC v8Stage III Penile Cancer AJCC v8Stage III Renal Cell Cancer AJCC v8Stage III Renal Pelvis and Ureter Cancer AJCC v8Stage III Renal Pelvis Cancer AJCC v8Stage III Ureter Cancer AJCC v8Stage III Urethral Cancer AJCC v8Stage IV Bladder Cancer AJCC v8Stage IV Penile Cancer AJCC v8Stage IV Renal Cell Cancer AJCC v8Stage IV Renal Pelvis and Ureter Cancer AJCC v8Stage IV Ureter Cancer AJCC v8Stage IV Urethral Cancer AJCC v8Ureter Urothelial CarcinomaUrethral Urothelial CarcinomaNCT02496208National Cancer Institute (NCI)152
Active, not recruiting
Phase 2
Cabozantinib In Combo With NIVO + IPI In Advanced NCCRCCPapillary Renal Cell CarcinomaUnclassified Renal Cell CarcinomaTranslocation Renal Cell CarcinomaChromophobe Renal Cell CarcinomaCollecting Duct Renal Cell CarcinomaRenal Cell CarcinomaUnresectable Advanced Renal Cell CarcinomaMetastatic Ncc Renal Cell CarcinomaNCT04413123Bradley A. McGregor, MD60
Recruiting
Phase 2
Testing the Effectiveness of Two Immunotherapy Drugs (Nivolumab and Ipilimumab) With One Anti-cancer Targeted Drug (Cabozantinib) for Rare Genitourinary TumorsBladder AdenocarcinomaBladder Clear Cell AdenocarcinomaBladder Mixed AdenocarcinomaBladder Neuroendocrine CarcinomaBladder Small Cell Neuroendocrine CarcinomaBladder Squamous Cell CarcinomaChromophobe Renal Cell CarcinomaCollecting Duct CarcinomaInvasive Bladder Giant Cell Urothelial CarcinomaInvasive Bladder Lymphoepithelioma-Like CarcinomaInvasive Bladder Nested Urothelial CarcinomaInvasive Bladder Plasmacytoid Urothelial CarcinomaInvasive Bladder Sarcomatoid Urothelial CarcinomaInvasive Bladder Urothelial CarcinomaKidney Medullary CarcinomaLarge Cell Neuroendocrine CarcinomaMalignant Testicular Leydig Cell TumorMalignant Testicular Sertoli Cell TumorMetastatic Bladder CarcinomaMetastatic Bladder Clear Cell (Glycogen-Rich) Urothelial CarcinomaMetastatic Bladder Giant Cell Urothelial CarcinomaMetastatic Bladder Large Cell Neuroendocrine CarcinomaMetastatic Bladder Lipid-Rich Urothelial CarcinomaMetastatic Bladder Micropapillary Urothelial CarcinomaMetastatic Bladder Plasmacytoid Urothelial CarcinomaMetastatic Bladder Sarcomatoid Urothelial CarcinomaMetastatic Bladder Small Cell Neuroendocrine CarcinomaMetastatic Bladder Squamous Cell CarcinomaMetastatic Chromophobe Renal Cell CarcinomaMetastatic Kidney Medullary CarcinomaMetastatic Malignant Genitourinary System NeoplasmMetastatic Papillary Renal Cell CarcinomaMetastatic Penile CarcinomaMetastatic Prostate Small Cell Neuroendocrine CarcinomaMetastatic Sarcomatoid Renal Cell CarcinomaMetastatic Urethral CarcinomaPapillary Renal Cell CarcinomaSarcomatoid Renal Cell CarcinomaStage IV Bladder Cancer AJCC v8Stage IV Penile Cancer AJCC v8Stage IV Renal Cell Cancer AJCC v8Stage IV Urethral Cancer AJCC v8Stage IVB Prostate Cancer AJCC v8Urachal AdenocarcinomaUrethral Clear Cell AdenocarcinomaNCT03866382National Cancer Institute (NCI)314
Active, not recruiting
Phase 1
A Study of Cabozantinib and Nivolumab With Radiation Therapy for People With Renal Cell Carcinoma That Has Spread to the BrainMetastatic Renal Cell CarcinomaBrain MetastasesNCT06132945Memorial Sloan Kettering Cancer Center2